Rinvoq Approved for Moderately to Severely Active Crohn Disease

The Food and Drug Administration (FDA) has approved Rinvoq^® (upadacitinib) for the treatment of adults with moderately to severely active Crohn disease who have had an inadequate response or intolerance to 1 or more tumor necrosis factor (TNF) blockers.

The approval was based on data from 2 randomized, double-blind, placebo-controlled phase 3 induction studies, U-EXCEED (ClinicalTrials.gov Identifier: NCT03345836) and U-EXCEL (ClinicalTrials.gov Identifier: NCT03345849), and one phase 3 maintenance study, U-ENDURE (ClinicalTrials.gov Identifier: NCT03345823).

The studies evaluated the efficacy and safety of upadacitinib in adults with moderately to severely active Crohn disease who had an inadequate response to or were intolerant of biologic therapy. In the induction studies, patients were randomly assigned 2:1 to receive upadacitinib 45mg or placebo once daily for 12 weeks. In the maintenance study, patients were re-randomized to receive upadacitinib 15mg, 30mg, or placebo once daily for up to 52 weeks. 

Findings showed that a greater proportion of patients treated with upadacitinib achieved clinical remission (measured by the Crohn Disease Activity Index [CDAI]) and endoscopic response (defined as a >50% decrease in Simple Endoscopic Score for Crohn Disease [SES-CD] from baseline of the induction study) compared with those who received placebo (coprimary endpoints):

• U-EXCEED Induction: Clinical remission per CDAI: 36% vs 18% at week 12 (P <.001); Endoscopic response: 34% vs 3% at week 12 (P <.001).
• U-EXCEL Induction: Clinical remission per CDAI: 46% vs 23% at week 12 (P <.001); Endoscopic response: 46% vs 13% at week 12 (P <.001).
• U-ENDURE Maintenance for upadacitinib 15mg and 30mg: Clinical remission per CDAI: 42% and 55% vs 14% at week 52 (P <.001); Endoscopic response: 28% and 41% vs 7% at week 52 (P <.001).

Findings from the maintenance study also showed that 19% and 30% of patients receiving upadacitinib 15mg and 30mg, respectively, achieved endoscopic remission compared with 5% of the placebo group. Corticosteroid-free remission was reported in 42% of patients in the upadacitinib 15mg group, 53% of patients in the upadacitinib 30mg group, and 14% of patients in the placebo group.

“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” said Edward V. Loftus, Jr, MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota and U-EXCEL study investigator.

The most common adverse reactions reported with upadacitinib in Crohn disease trials were upper respiratory tract infections, anemia, fever, acne, herpes zoster, and headache. The prescribing information for Rinvoq, a selective and reversible Janus kinase (JAK) inhibitor, also includes a Boxed Warning regarding the risks of serious infection, mortality, malignancy, major adverse cardiovascular events and thrombosis.

Rinvoq is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn disease, or with potent immunosuppressants such as azathioprine and cyclosporine.